PNEUMOCOCCAL DISEASE IN SOUTH ASIA: THE PROMISE OF VACCINES

Pre-ISPPD9 South Asia Symposium

For the first time in its history, the International Symposium on Pneumococci and Pneumococcal Disease (ISPPD), the preeminent global conference, was held in Asia in March 2014. Nearly 1,000 scientists and public health experts from around the world convened March 9-13 in Hyderabad, India to discuss the latest developments in pneumococcal research and pneumococcal disease prevention.

Given the high burden of pneumococcal disease in India and South Asia, and the need for action for prevention and control, IVAC and INCLEN Trust hosted a pre-ISPPD symposium titled “Pneumococcal Disease in South Asia: The Promise of Vaccines.” The meeting objectives included:

Review available data on pneumococcal disease burden in South Asia

Review the status of pneumococcal conjugate vaccine (PCV) introduction and impact in South Asia

A wealth of data was shared, and there was consensus from symposium participants that there is sufficient evidence of pneumococcal disease burden in South Asia to warrant introduction of PCV. Like the rest of the world, South Asia has a significant burden of pneumonia caused by pneumococcus. Many countries around the world have introduced PCV and documented dramatic successes in reducing invasive pneumococcal disease (IPD), pneumonia, meningitis, and other illnesses caused by pneumoccus. In addition to protecting vaccinated children, studies demonstrate that PCV results in significant herd protection for unvaccinated individuals. Pakistan was the first South Asian country to introduce PCV nationally in 2012. Symposium participants from Pakistan, as well as The Philippines and Laos PDR presented case studies of vaccine introduction and impact in their countries. Several other South Asian countries are now planning introductions, including Nepal, Bangladesh, Mongolia, and Cambodia. Symposium participants agreed the vaccine could have a great impact across the region.

The presentations and slides from the symposium are summarized below (click on the links to view summary).

Presentation Summaries

Thomas Cherian, World Health Organization (WHO)

Reviewing the global data, Streptococcus pneumoniae (Spn or pneumococcus) is an important cause of serious disease in children worldwide. Establishing Spn etiology in pneumonia is very challenging; culture positive Spn disease represents only the “tip of the iceberg”. New diagnostics (latex agglutination, polymerase chain reaction) are improving bacterial etiology, including Spn, particularly in Asia where traditional cultures historically yielded low results. Nasopharyngeal (NP) carriage occurs earlier in childhood in lower socio-economic countries. Pneumococcus is a major cause of childhood bacterial meningitis and has a high fatality rate compared to other etiologies. Pneumococcal conjugate vaccines (PCVs) cover approximately 70-74% of serotypes in Asia for PCV10 and PCV13 respectively. Data demonstrates regional, temporal, and syndrome serotype distribution variation.

In sum, synthesized, available data, evidence supports the conclusion that Spn is an important cause of child morbidity and mortality in South Asia. The Spn epidemiology in South Asia is comparable to Africa and worldwide, pre-vaccine introduction.

Bangladesh and Nepal will introduce PCV this year (2014), and Myanmar plans to introduce PCV in 2016. Regional and global data are considered in NTAGI decision making, demonstrating the need for epidemiologic surveillance data in vaccine policies. Early on, lack of regional epidemiological/economic evidence slowed PCV introduction in the South-East Asia region. Challenges include funding, access to and use of newer diagnostic technologies, surveillance standardization, national ownership, and sustainability. With external and national funding, some local surveillance sites were established. Despite the limited scope of sentinel surveillance data, these data in conjunction with global evidence proved useful. There is potential with post-introduction impact evaluation studies for countries to expand and take ownership of these surveillance activities.

Rajesh Kumar, Professor, Postgraduate Institute of Medical Education & Research (PGIMER) School of Public Health (India)

The presentation gives an overview of the history, development and efficacy of pneumococcal vaccines. Based on a Cochrane Systematic Review (Lucero, 2009), rates of PCV efficacy are approximately 80% (95% confidence interval: 58-90%) for vaccine serotypes, 58% for all serotypes, 27% for radiological pneumonia, and 6% for clinical pneumonia. PCV is also effective in reducing viral pneumonia hospitalizations (as severity is related to co-infection with Spn), otitis media, and NP carriage. The vaccine is well tolerated and has an acceptable safety profile. In India, invasive pneumococcal disease has a high case fatality rate (25-30%) (Thomas, 2013); pneumococcus is a main pathogen in community-acquired pneumonia (61.6%) (Mani, 2007); and rates of NP carriage (28%) and antibiotic resistance in HIV-infected children are high (Bhattacharya, 2011). India needs to introduce PCV in the national immunization schedule, and there is a continuing need for surveillance and improved diagnostic tools to monitor the effects on disease and serotype distribution.

Brief Overview of PCV Impact Studies in Kilifi, Kenya

Preliminary data from studies in Kilifi demonstrate the impressive, positive impact on nasopharyngeal carriage in all ages, on vaccine-type IPD in children under five years, in non-target age groups (demonstrating indirect effects/herd immunity), and in clinical pneumonia. Summaries of the study results can be viewed on the Kilifi project website. These results will soon be published.

Pakistan was the first South Asian country to introduce PCV, in October 2012. Meningitis surveillance was conducted (initially with GAVI support) for a few years before PCV introduction, and government support surveillance for the impact of PCV on IPD and NP carriage is currently ongoing. Surveillance had low direct detection of Spn, but adjustments for case recruitment and diagnostic sensitivity showed Pakistan had Spn meningitis rates similar to Western countries in the pre-vaccine era. IBD and NP carriage studies were also conducted. Haemophilus influenzae type b (Hib) vaccine effectiveness studies were also presented. The data demonstrate the positive impact of Hib and PCV vaccines in reducing meningitis caused by the respective bacteria. A GAVI-sponsored study on the impact of PCV 10 in Sindh (Pakistan) continues and focuses on determining coverage rates and evaluating efforts to improve coverage in selected districts. The data from these studies will be published in 2015-2016.

Eric Tayag, Assistant Secretary, Department of Health (Philippines)

The burden of pneumonia was recognized in the Philippines, and multiple partners in the context of achieving millennium development goals (MDGs) and Universal Health Coverage advocated for PCV introduction. With a birth cohort of over 1.7 million, pneumonia was recognized as the leading cause of illness, hospitalization, and death in children under 5 years. The average number of under-five pneumonia cases in 2010 and 2011 was over 340,000 per year. Building upon disease burden evidence, communication and advocacy initiatives, professional organizations and partners, the vaccine was introduced in 2013 in a phased manner due to the high cost of PCV, targeting high-risk children. The Philippines attributes its PCV policy and program success to enhanced IPD surveillance, “cost-free” impact studies, demonstrating the benefits of vaccines balanced with integrated management of childhood illness, accessing reduced-price vaccines from the world market, promoting social benefits of vaccination, and engaging partners to achieve common goals for child survival.

Cynthia Whitney, Centers for Disease Control and Prevention (USA)

Data from the U.S. and other countries show indirect protection with PCV: faster than expected decrease in childhood IPD, decrease in IPD among children outside vaccinated age group, drop in carriage of vaccine-type strains, and decrease in adult disease. Indirect effects would be expected in South Asia; however, indirect impact will depend upon vaccination coverage and catch-up programs, as well as on the distribution of vaccine-type disease caused in different age populations. The indirect protection of PCV is recognized as a powerful driver of PCV program benefits.

The presentation reviewed the data on the impact of PCV, including a discussion of serotype 19A. Antibiotic use is common and increasing in South Asia, and a combination of PCV and policies for judicious use could help prevent the spread of antibiotic resistance. Serotype coverage is approximately 70% for PCV 10 and 74% for PCV 13 in South Asia. One study shows that PCV 13 covers 67% of serotypes causing IPD in Bangladesh. South Asian countries have the opportunity to use PCV introduction to gather good data on the impact of PCV on Spn epidemiology. Well-designed studies should be planned and implemented around PCV introduction.

Lao introduced PCV in November 2013 in Vientiane capital and Vientiane province with GAVI support. National introduction is planned in 2014. Low documented IPD rates (from culture studies) did not hinder introduction. The government recognized that pneumonia was the leading cause of mortality/morbidity in children, access to antibiotics was limited in many communities, and community demand for a vaccine was good. Lao faces a challenge in measuring vaccine impact as there was no baseline data available when the decision was made to introduce. Given the high mortality and morbidity rates, policy makers prioritized access to the vaccine.

Shrijana Shrestha, Dean of School of Medicine, Patan Academy of Health Sciences (Nepal)

Patan Hospital has been a surveillance site for several international surveillance networks, including the South Asian Pneumococcal Network Alliance (SAPNA), PneumoADIP, and WHO SEARO. Serotypes 1 and 5 cause the most disease, but are often not found in carriage. Studies evaluated two vs. three doses and found that 2+1 dose regimens (6, 14 weeks and 9 months) give better protection measured at two to four years of age for the leading serotypes. Studies funded by GAVI are currently being conducted to measure the impact of PCV introduction on NP carriage, meningitis, and pneumonia hospitalizations (using hospital records).

Though India’s under-five mortality rate has significantly declined from 1990, pneumonia and diarrhea cause significant morbidity and mortality among Indian children. In India, 23% of all childhood deaths are caused by pneumonia, and India alone accounts for 25% of global pneumonia deaths. Many risk factors are common to both pneumonia and diarrhea, and addressing them through an integrated approach will lead to dual benefits. While progress has been made, improvements have not been uniform. Disparities exist across states and within states by districts. Currently, India has identified 184 districts across 28 states as high priority. In order to address critical gaps and ensure interventions reach those most in need, investments need to match disease burden while also prioritizing hard to reach areas and marginalized groups. In addition, policies need to be successfully implemented through action plans at state and local levels. To reduce pneumonia disease burden, many initiatives are underway and technical guidelines for pneumonia management are being finalized. Overall, a comprehensive approach to address neonatal and child health including vaccines will be important. Vaccines, such as Hib, measles, and PCV, are vital to prevent pneumonia and child mortality and illness.